Cancer

Cancer Research

Researchers in the HMRI Cancer research program study many different types of cancers using multidisciplinary and collaborative techniques which make them a diverse and well-rounded translational research group.

Cancer is a major cause of disability and death in Australia with an estimate of 130,470 new cases of cancer diagnosed this year. It is projected that by 2020, this number will rise to 150,000. (Source – Cancer Council Australia)

Whilst 66% of people diagnosed with cancer in Australia are still alive five years after diagnosis, cancer is still the cause of 3 out every 10 deaths in Australia. (Source – Cancer Council Australia)

Researchers in the HMRI Cancer research program work in a number of specialised areas to understand the molecular and cellular mechanisms that underlie the development of cancer and find ways to translate these findings into the clinic to improve patient outcomes. Similarly, ideas and research focuses that are generated in the clinic are fed back to laboratory and preclinical scientists who work continually to improve both the care and treatment of patients. This bi-directional approach makes Hunter cancer researchers unique and successful in their field across the nation and indeed the globe.

Research has found that at least one in three of cancer cases are preventable, highlighting the need for effective research into the causes, intervention programs and treatment options for the thousands of Australians diagnosed with cancer each year. (Source – Cancer Council Australia)

Hunter researchers can access one of the nation’s largest biobanks of cancer tissue and specimens which are catalogued and organised so that researchers from a wide variety of disciplines can research their particular focus without the need to recruit a new sample of patients and collect tissues. This is both an efficient and cost effective way to collect samples, making it an extremely valuable resource for researchers and clinicians alike.

Hunter researchers are interested in researching many different aspects and types of cancer including:

2018

Multiple myeloma (MM) is a cancer of plasma cells, which are mature white blood cells within the bone marrow. The disease causes bone pain, fractures, infections, anaemia and renal failure. It typically affects people over the age of 60, with about 1700 new diagnoses each year in Australia.[1] It is incurable and carries a life expectancy of 2-7 years depending on the aggressiveness of the tumour cells.

AML (acute myeloid leukemia) is a very aggressive form of leukemia. Tumour suppressor proteins are critically important for normal healthy cells to be protected from genetic mutations. However in AML mutations occur in the genes responsible for stem growth and cell differentiation. The growth of the blood stem cells is accelerated but their differentiation into other cells is inhibited.

Ovarian cancer is usually treated with a chemotherapy drug called cisplatin which works by damaging DNA so much that the tumour cells die. Cisplatin is used to treat a wide variety of tumours in addition to ovarian cancer including, testicular, head and neck and non-small cell lung cancer. In addition, it forms the basis of most combined treatment regimes (where 2 or more drugs are used in combination). The downside to cisplatin is that it is extremely toxic and although some patients benefit substantially from treatment, a large proportion suffer the toxic side effects without any therapeutic benefit. We are aiming to develop a personal test to determine if cisplatin is likely to be effective for an individual’s ovarian cancer, so that the toxic side effects can be avoided if the drug is not going to work.

Treatment for the most common and deadly form of blood cancer (acute myeloid leukaemia) hasn’t changed in over 40 years. New treatments fail because leukaemia’s genes have a high propensity to mutate, causing rapid resistance to therapies. We have discovered that these gene mutations cause chemical-modifications to the cells defence systems. Unrestrained growth of these cancerous cells results in the production of excess reactive by-products that progressively change the cancer, making long-term treatment response and patient survival unlikely. This project will test whether targeting these chemical-modifications will be a more effective new treatment strategy.

Half of all malignant childhood gliomas arise in the brainstem, most frequently in the ventral pons as diffuse intrinsic pontine gliomas (DIPG). The anatomical location of the tumour precludes surgical resection, leaving only radiotherapy as the established therapy. Unfortunately, radiotherapy is only temporarily beneficial, and occasionally completely fails, leaving patients without treatment option.

A good quality of life and long survival are standard societal expectations of health care, but sadly this is not the norm for patients with brain cancer (glioma). Surgery, radiotherapy, and chemotherapy are current therapies which target cancer cells directly but have shown limited benefit to patients long-term.

AML (acute myeloid leukemia) is a very aggressive form of leukemia. Tumour suppressor proteins are critically important for normal healthy cells to be protected from genetic mutations. However in AML mutations occur in the genes responsible for stem growth and cell differentiation. The growth of the blood stem cells is accelerated but their differentiation into other cells is inhibited.

A very useful and convenient method used in many fields of medical research involves growing cells in the laboratory. Cells are ""cultured"" in plastic dishes in incubators that provide an environment warmed to body temperature, 37 degrees Celsius. Human cells also require carbon dioxide to grow and this is added to the ambient air in the incubator. This kind of cell culture has been used for over a century and has been accepted as the standard way of growing cells in the laboratory. This method is very important and useful in cancer research.

Ovarian cancer is usually treated with a chemotherapy drug called cisplatin which works by damaging DNA so much that the tumour cells die. Cisplatin is used to treat a wide variety of tumours in addition to ovarian cancer including, testicular, head and neck and non-small cell lung cancer. In addition, it forms the basis of most combined treatment regimes (where 2 or more drugs are used in combination). The downside to cisplatin is that it is extremely toxic and although some patients benefit substantially from treatment, a large proportion suffer the toxic side effects without any therapeutic benefit. We are aiming to develop a personal test to determine if cisplatin is likely to be effective for an individual’s ovarian cancer, so that the toxic side effects can be avoided if the drug is not going to work.

Childhood brain tumours (CBTs) are the second most common paediatric malignancy after leukaemia and the leading cause of cancer-related death in children under the age of 19 years. CBTs can be classified into several distinct groups based on their cell morphology and malignant potential. All CBTs have a neuroepithelial origin and are thought to be derived from neural stem cells that can differentiate into a variety of different tumour types such as astrocytic tumours, oligodendroglial tumours, mixed gliomas, ependymal tumours, neuronal and mixed tumours, neuronal and glial tumours, embryonal tumours and primitive neuroectodermal tumours. By far the most frequent are gliomas, followed by embryonal tumours.

Multiple myeloma (MM) is a cancer of plasma cells, which are mature white blood cells within the bone marrow. The disease causes bone pain and weakening which often leads to fractures. It typically affects people over the age of 60, with about 1700 new diagnoses each year in Australia. It is incurable and carries a life expectancy of 2-7 years depending on the aggressiveness of the tumour cells. Although the actual cause of MM is unknown, it is often preceded by less severe forms of the disease called monoclonal gammopathy of undetermined significance (MGUS), and smouldering multiple myeloma (SMM). However, not everyone with these early stages will develop MM, and it is not clear what drives progression of the disease.

Shwachman-Diamond-Syndrome (SDS) is an inherited disease that affects 1 in every 76,000 children. Dysfunction of the child’s blood and circulatory system occurs in nearly all patients, causing increased rates of infection and decreased capacity to transport oxygen. Unfortunately, the overall survival of a young person with SDS is only 35 years, and this is attributed to sepsis, organ failure and most frequently the development of leukaemia.

Breast cancer can spread to other organs in the body including the lungs, liver and bones. Unfortunately, this type of ‘metastatic’ breast cancer is difficult to treat, and the majority of patients die within 5 years of diagnosis. We urgently need new ways to prevent, detect and treat metastatic breast cancer, in order to save the lives of breast cancer patients.

Recent discoveries, including from our laboratory, have revealed the important role played by nerves in cancer progression, and targeting nerve outgrowth in the tumour microenvironment is an emerging innovative strategy in oncology. In pancreatic cancer, it has been shown that the outgrowth of sensory nerves in the microenvironment is necessary to cancer progression and stimulates pain.

The chemotherapy drug, 5-fluorouracil (5-FU), or its oral pro-drug capecitabine, are commonly used in treating oesophageal and gastric cancer. The dose a patient receives is currently determined using body surface area. This approach, however, produces outcomes ranging from poor efficacy to toxicity including mouth ulcers, diarrhoea or life threatening febrile neutropenia.

Faecal occult blood testing (FOBT) is used as a population based method to identify people over the age of 50 years with colorectal cancer. Fortunately, the majority of patients with a positive FOBT do not have colorectal cancer and only about 5% are diagnosed with CRC and 30% with polyps after colonoscopy. Colonoscopy is not without risk and even in the most experienced hands there is a morbidity associated with this procedure.

It has become apparent over the last decade that a class of molecules called long noncoding RNAs (lncRNA), which were originally thought to be ‘junk’ in mammalian cells, play a major role in controlling gene expression and disease.

Cancer is the most common cause of childhood disease-related deaths, with leukaemia the most common childhood cancer in Australia. The two most common forms of leukaemia in children are acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Whilst remission is achievable in over 95% of ALL cases, 1/3 of patients will relapse within 5 to 10 years, and these children will not be long-term survivors. AML accounts for 20% of all childhood leukaemias, and the outlook for children diagnosed with AML is much worse, with only approximately half of children surviving for 5 years post-diagnosis.

Treatment for the most common and deadly form of blood cancer (acute myeloid leukaemia) hasn’t changed in over 40 years. New treatments fail because leukaemia’s genes have a high propensity to mutate, causing rapid resistance to therapies. We have discovered that these gene mutations cause chemical-modifications to the cells defence systems. Unrestrained growth of these cancerous cells results in the production of excess reactive by-products that progressively change the cancer, making long-term treatment response and patient survival unlikely. This project will test whether targeting these chemical-modifications will be a more effective new treatment strategy.

This is a versatile, automated platform for quantification and quality control of DNA, RNA and proteins. It can process up to 16 samples in less than two minutes. This instrument does not require cleaning action so there are no chances of contamination from remnants of RNA from the previous sample. Once loaded the sample remains saved up to two hours as there is no evaporation loss. This machine provides the option for flexible input & multi-sample read. The analysis is automatic and a digital report is generated which can be exported to a USB.

Ovarian cancer is most commonly treated with a chemotherapy drug called cisplatin. Cisplatin works by damaging DNA so much that the tumour cells die. It forms the basis of most combined treatment regimes (where two or more drugs are used in combination). The downside to cisplatin is that it is extremely toxic and although some patients benefit substantially from treatment, a large proportion suffer the toxic side effects without any therapeutic benefit.

Underpinning Australian brain cancer research: creating the resources essential to accelerate access and sharing of biospecimens and associated clinical data vital to advancing research in brain cancer.

Researchers:

Dr Raymond Cook, A/Prof Jennifer Byrne

Description:

Brain cancer is one of the most under researched of all cancers, little is known about its cause or how to treat it, resulting in very low survival rates. Brain cancer research increasingly relies on collections of tumour samples and associated data (biobanks). Due to the location of brain cancer, and its rare nature, obtaining sufficient clinical samples is difficult. Furthermore, brain cancer biobanks across Australia are geographically and operationally disparate, and to date there has been no effort to coordinate them.

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia, and it has the lowest 5yr survival rate at a dismal 24%. Recently, improved technologies have enabled researchers to identify a number of mutations that recur in AML.

Metastatic pancreatic cancer has a low survival rate and even with the best existing therapies the survival is less than a year. Despite advances in treatments and outcomes for other cancers, this has not happened for pancreatic cancer with no advances in mortality reduction observed over the past decade. This grim outlook drives our research, which focuses on developing novel diagnostic strategies for pancreatic cancer.

The Bioimpedence Scales are essentially a pair of 'fancy' scales that measure the density of body tissue to predict body mass - amount and composition. This is important because we know the relative amounts of fat and lean tissue in a patient affect how much of a drug gets to a particular site like the tumour and also determines how long it stays there and how the drug is released over time.

Annually there are 2,000 new cases of brain cancer in Australia. Prognosis for people with brain cancer is dire. Glioblastoma (GBM) is the most common brain tumour, the most lethal and difficult to treat.

Underpinning Australian brain cancer research: creating the resources essential to accelerate access and sharing of biospecimens and associated clinical data vital to advancing research in brain cancer.

Researchers:

Dr Raymond Cook, Robyn Leonard, Jennifer Byrne

Description:

Brain Cancer Biobanking Australia (BCBA) is an initiative established to facilitate the networking of both adult and paediatric brain cancer biobanking operations Australia-wide with the aim of providing researchers with access to the number, quality and type of tissue samples and associated data

Project Goal - To develop a test for predicting ovarian cancer response/resistance to cisplatin chemotherapy that can be quickly implemented in clincial centres. Such a test would let the doctor know that the patient is becoming resistant to cisplatin chemotherapy. At this stage there is no test available meaning some people remain on the wrong treatment protocol for the course of their treatment, suffereing toxic side effects for no benefit. The sooner treatment is switched the higher the chance that the patient will respond.

Annually there are 2,000 new cases of brain cancer in Australia. Prognosis for people with brain cancer is dire. It is the highest cause of death in 0-39 age group with a 5-year survival rate of 19%. Brain cancer results in 5,000 hospitalisations per year (average stay 12.5 days, the longest of any cancer) and has the highest lifetime cost per patient of $1.89m [1].

Cancer is one of the leading causes of death worldwide. Brain cancer is the 15th most common cancer in the world, and has one of the worst survival rates of all cancer types, with only approximately half of patients surviving for one year post-diagnosis. This poor survival rate highlights that new treatments for brain cancer are urgently required.

AML (acute myeloid leukemia) is a very aggressive form of leukemia. Tumour suppressor proteins are critically important for normal healthy cells to be protected from genetic mutations. However in AML mutations occur in the genes responsible for stem growth and cell differentiation.

Cancer immunotherapy is a therapeutic strategy that harnesses cancer patients own immune system to specifically target cancer cells. A new class of newly developed drugs in cancer immunotherapy (called immune checkpoint inhibitors) can cause long lasting regression of tumors and prevent relapse but only a small number of patients currently benefit from these drugs.

2015

Cancer is one of the leading causes of death worldwide. Brain cancer is the 15th most common cancer in the world, and has one of the worst survival rates of all cancer types, with only approximately half of patients surviving for one year post-diagnosis. This poor survival rate highlights that new treatments for brain cancer are urgently required.

Annually there are 2,000 new cases of brain cancer in Australia. Prognosis for people with brain cancer is dire. It is the highest cause of death in 0-39 age group with a 5-year survival rate of 19%. Brain cancer results in 5,000 hospitalisations per year (average stay 12.5 days, the longest of any cancer) and has the highest lifetime cost per patient of $1.89m.

Matt will use his Jennie Thomas medical research travel grant to attend the European Molecular Biology Organisation (EMBO) Targeted Proteomics Course to be held at the Centre for Genomic Regulation, Barcelona, Spain where he will learn the theory and methods necessary to implement targeted proteomics workflow on patient samples which he will then pass onto the researchers of HMRI.

American Society for Therapeutic Radiation Oncology Meeting, San Antonio, Texas, 18-21 October 2015

Researchers:

Dr Mike Fay

Description:

Dr Mike Fay is a Calvary Mater Newcastle radiation oncologist and used his Mark Hughes Foundation Travel Grant to attend the ‘Technology meets patient care’ American Society for Therapeutic Radiation Oncology (ASTRO) meeting in San Antonio, Texas, from October 18-21. This grant will help Mike in his goal to develop better brain tumour imaging and therapeutics.

Dr Adrian Lee is also attending Dr Lee the COGNO Annual Scientific Meeting in Brisbane this month to present data on the use of the drug Bevacizumab in Glioma (a tumour that begins in the brain’s glial cells).

Pia Laegdsgaard will use her Mark Hughes Foundation travel grant to present at the COGNO Annual Scientific Meeting in Brisbane this month. Pia has developed a research poster outlining the processes involved in establishing and managing the brain cancer facility as part of the HCB.

2014

Dr Gedye’s basic laboratory research within the HMRI Building will focus on ways of targeting these more aggressive kidney cancer cells, and hopefully lead to novel combinations of old and new drugs to work with the medications routinely used in the clinic.

The Breast Cancer Translational Research Laboratory J.C. Heuson based at Institut Bordet, in Brussels, uses several molecular approaches to gain a better understanding of breast tumorigenesis, metastasis, and drug resistance.

Conference: San Antonio Breast Cancer Symposium (SABCS) 2014SABCS is a highly regarded annual meeting that aims to provide high quality information on experimental biology, prevention, diagnosis and therapy of breast cancer to an audience that focuses on breast cancer research.

Breast cancer is the most common cancer in women, with 1 in 9 women diagnosed in their lifetime. Estrogen and an important gene known to stop cancer development (p53) are essential for normal breast growth.

Fluoropyrimidines (5-FU and capecitabine) are anticancer drugs commonly used in a range of cancers including oesophageal, gastric and colorectal cancers. Their toxicity is unpredictable, leading to significant and sometimes life-threatening side effects. Pharmacokinetics (steady state plasma level, area under the curve, etc.) varies between patients by a factor of 5-10, and this is also unpredictable. Although therapeutic drug monitoring might allow better management of pharmacokinetic variability by rapid dose adjustment, it is labour-intensive and time-consuming.

Brain tumours are the second most frequent cancer diagnosed in children yet very little is known about the risk factors associated with their occurrence or what events are necessary for their progression.

Androgen suppression (AS) used prior to or following RT for locally advanced prostate cancer reduces cancerous recurrence in the prostate and at metastatic sites, thereby also reducing prostate cancer mortality.

Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-related death rates. While the prognosis is good if the cancer is limited to the breast; once a patient has developed metastatic disease they are essentially incurable.

Breast cancer is the most common cancer that develops in women. A gene known to suppress cancer development (p53) is essential for the normal growth of the breast. Loss of this control is associated with poor outcome in breast cancer.

2010

The HMRI Pulse Education Prize will enable Dr Avery-Kiejda to attend the Keystone Symposia MicroRNAs and Non-Coding RNAs and Cancer to be held 11-16th February 2011 in Banff, Alberta. This meeting will give Dr Avery-Kiejda with the opportunity to present the findings of her breast cancer studies and to meet and communicate with internationally renowned cancer researchers to further establish collaborations with prominent leaders in the field.